Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Dec 31:15:2938-44.

Upregulated IL-21 and IL-21 receptor expression is involved in experimental autoimmune uveitis (EAU)

Lan Liu  1 , Yongfeng Xu, Jianyong Wang, Huiyan Li
Affiliations

Upregulated IL-21 and IL-21 receptor expression is involved in experimental autoimmune uveitis (EAU)

Lan Liu et al. Mol Vis. .

Abstract

Purpose: Interleukin (IL)-21 has recently been shown to play a vital role in the development of many autoimmune diseases. Our study is designed to investigate the alteration and possible function of IL-21 in the development of an experimental autoimmune uveitis (EAU) model.

Methods: EAU was induced in B10.RIII mice by subcutaneous injection of interphotoreceptor retinoid-binding protein (IRBP) 161-180 emulsified with complete Freund's adjuvant (CFA) and evaluated by clinical and histopathologic observation. IL-21 and IL-21R mRNA expressions in cells of draining lymph node (DLN) and spleen in EAU and control mice were determined by reverse transcription-PCR. The frequencies of interleukin-21 receptor positive cells were also examined using flow cytometry. IL-17 levels in the supernatant of the cell culture upon IL-21 stimulation were assayed by enzyme-linked immunosorbent assay.

Results: Results showed that EAU was successfully induced by IRBP161-180. Expression of IL-21 mRNA was significantly increased in cells of DLN and spleen in EAU compared with recovery phase mice and normal controls. IL-21R was also found upregulated in DLN and spleen cells of EAU mice by reverse transcription-PCR and flow cytometry. Cells in EAU cultured with IL-21 combined with transforming growth factor-beta induced increased production of IL-17.

Conclusion: The findings revealed that increased IL-21 and IL-21R expression may be involved in the development of EAU, possibly by promoting IL-17 secretion.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Histopathologic features of the eyes of experimental autoimmune uveitis (EAU) mice. Eyes were enucleated from EAU and complete Freund’s adjuvant (CFA) control mice on day 14 after immunization. Sections (5 µm) were cut through the pupillary–optic nerve plane and stained with hematoxylin and eosin. A: Eye of CFA controls. The retina layers are well ordered and preserved. B: Eye of EAU mice. The normal structure of the retina is disorganized. Inflammatory cells infiltrate the ciliary body, choroid, vitreous and retina. Vasculitis, granuloma formation, and retinal folding are visible, and the photoreceptor layer is damaged. The scale bar=50 µm.
Figure 2
Figure 2
Reverse transcription-PCR analysis of interleukin-21 in the cells of spleen and draining lymph node in experimental autoimmune uveitis, recovery phase and control mice. mRNA of IL-21 in splenocytes and draining lymph node (DLN) cells of EAU, recovery phase mice, and control mice were extracted and measured through RT–PCR. A: IL-21 mRNA of DLN cells in EAU, recovery phase mice, and control mice. B: IL-21 mRNA of spleen cells in EAU, recovery phase mice, and control mice. C: The relative IL-21 mRNA levels were determined as the ratio of the IL-21 PCR product over the β-actin product. Data are presented as mean±standard deviation; n=6 per group.
Figure 3
Figure 3
Reverse transcription-PCR analysis of interleukin-21 receptor in the cells of spleen and draining lymph node in experimental autoimmune uveitis, recovery phase and control mice. mRNA of IL-21R in splenocytes and draining lymph node (DLN) cells of EAU, recovery phase mice, and control mice were extracted and measured through RT–PCR. A: IL-21R mRNA of DLN cells in EAU, recovery phase mice, and control mice. B: IL-21R mRNA of spleen cells in EAU, recovery phase mice, and control mice. C: The relative IL-21 mRNA levels were determined as the ratio of the IL-21 PCR product over the β-actin product. Data are presented as mean±standard deviation; n=6 per group.
Figure 4
Figure 4
The percentage of interleukin-21 receptor positive cells from draining lymph node of experimental autoimmune uveitis and control mice. The isolated DLN cells were stained with anti-CD4, anti-CD8, and anti-IL-21R Ab for 0.5 h for the analysis of surface markers. A: Dot plots of IL-21R+ cells in CD4+ and CD8+ cells of EAU and control mice. Data shown are representative of six independent experiments. B: Percentages of IL-21R+ cells in CD4+ T cells of EAU and control mice. C: Percentages of IL-21R+ cells in CD8+ T cells. Data are presented as mean±standard deviation; n=6 per group.
Figure 5
Figure 5
Interleukin-17 production in the culture supernatant of experimental autoimmune uveitis and control mice. Cells from DLN and spleen were cultured with or without stimulation. The concentration of IL-17 in the supernatant was detected by ELISA. A: IL-17 production by DLN and spleen cells in EAU and control mice without stimulation. B: IL-17 production by DLN and spleen cells after IL-21 combined with or without TGF-β stimulation. Data are presented as mean±standard deviation; n=6 per group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Luger D, Silver PB, Tang J, Cua D, Chen Z, Iwakura Y, Bowman EP, Sgambellone NM, Chan CC, Caspi RR. Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med. 2008;205:799–810. - PMC - PubMed
    1. Tarrant TK, Silver PB, Chan CC, Wiggert B, Caspi RR. Endogenous IL-12 is required for induction and expression of experimental autoimmune uveitis. J Immunol. 1998;161:122–7. - PubMed
    1. Tarrant TK, Silver PB, Wahlsten JL, Rizzo LV, Chan CC, Wiggert B, Caspi RR. Interleukin 12 protects from a T helper type 1-mediated autoimmune disease, experimental autoimmune uveitis, through a mechanism involving interferon gamma, nitric oxide, and apoptosis. J Exp Med. 1999;189:219–30. - PMC - PubMed
    1. Jones LS, Rizzo LV, Agarwal RK, Tarrant TK, Chan CC, Wiggert B, Caspi RR. IFN-gamma-deficient mice develop experimental autoimmune uveitis in the context of a deviant effector response. J Immunol. 1997;158:5997–6005. - PubMed
    1. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–32. - PubMed

MeSH terms

LinkOut - more resources